Given the substantial health risks associated with concurrent alcohol and tobacco use (Rosengren et al., 1988), there has been a growing effort to address smoking cessation in those experiencing alcohol problems. Non-dependent hazardous drinkers have high rates of concurrent smoking and represent 80% of those who experience alcohol-related problems. Little is known about how best to promote smoking cessation in this population of drinkers who are at increased risk for poor smoking cessation outcomes. Pharmacotherapies for smoking cessation may promote improved quit rates in hazardous drinking smokers by reducing alcohol reactivity and consumption, thereby attenuating the ability of alcohol to prompt smoking relapse. Support for this project comes from a study by our group (R03AA013622-McKee) where we examined whether transdermal nicotine replacement (Omg,21 mg) altered reactivity to a fixed low dose of alcohol and subsequent ad-libitum consumption in moderate to heavy drinkers. Results demonstrated that 21 mg nicotine patch, compared to 6 hours of nicotine deprivation (placebo patch), decreased reactivity to the priming drink and reduced subsequent ad-libitum consumption. Current clinical practice guidelines indicate that combined nicotine replacement therapy (e.g., patch + nasal spray) and bupropion are two of the most efficacious pharmacotherapies available for smoking cessation. However, there is no research to date that has examined the effect of these two smoking cessation treatments on alcohol reactivity and self-administration behavior. Using similar procedures to our completed R03 project, the primary aim of STUDY 1 will be to examine whether 21mg patch + nicotine spray, compared to 21 mg patch + placebo spray, alters reactivity to alcohol (.03g/dl priming drink) and subsequent ad-libitum drinking in individuals who are non-depndent hazardous drinking smokers. Specifically we will examine the effect of combined nicotine replacement on 1) ad-libitum alcohol consumption and alcohol craving, 2) tobacco craving and nicotine withdrawal, and 3) subjective intoxication and mood. STUDY 2 will be of similar design and aims examining bupropion (SOOmg vs. Omg). This proposal will have important treatment implications for improving rates of smoking cessation in hazardous drinkers and will contribute to the understanding of alcohol-nicotine interactions.